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H3K27me3 conditions chemotolerance in triple-negative breast cancer [CUT&TAG]

ABSTRACT: H3K27me3 conditions chemotolerance in triple-negative breast cancer [CUT&TAG]

PROVIDER: PRJNA776906 | ENA |

REPOSITORIES: ENA

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H3K27me3 conditions chemotolerance in triple-negative breast cancer [CUT&TAG]

Project description:Triple-negative breast cancer is associated with the worst prognosis and the highest risk of recurrence among all breast cancer subtypes1. Residual disease, formed by cancer cells persistent to chemotherapy, remains the major clinical challenge towards full cure2,3. There is now consensus that non-genetic processes contribute to chemoresistance in various tumor types, notably through the initial emergence of a reversible chemotolerant state4–6. Understanding non-genetic tumor evolution stands now as a prerequisite for the design of relevant combinatorial approaches to delay recurrence. Here we show that the repressive histone mark H3K27me3 is a determinant of cell fate under chemotherapy exposure, monitoring epigenomes, transcriptomes and lineage with single-cell resolution. We identify a reservoir of persister basal cells with EMT markers and activated TGF-β pathway leading to multiple chemoresistance phenotypes. We demonstrate that, in unchallenged cells, H3K27 methylation is a lock to the expression program of persister cells. Promoters are primed with both H3K4me3 and H3K27me3, and removing H3K27me3 is sufficient for their transcriptional activation. Leveraging lineage barcoding, we show that depleting H3K27me3 alters tumor cell fate under chemotherapy insult - a wider variety of tumor cells tolerate chemotherapy. Our results highlight how chromatin landscapes shape the potential of unchallenged cancer cells to respond to therapeutic stress and pave the way for combinatorial therapy with modulators of chromatin.

2022-02-15 | GSE186966 | GEO

H3K27me3 conditions chemotolerance in triple-negative breast cancer

Project description:H3K27me3 conditions chemotolerance in triple-negative breast cancer

| PRJNA691624 | ENA

H3K27me3 conditions chemotolerance in triple-negative breast cancer [WES]

Project description:H3K27me3 conditions chemotolerance in triple-negative breast cancer [WES]

| PRJNA807278 | ENA

H3K27me3 conditions chemotolerance in triple-negative breast cancer.

Project description:The persistence of cancer cells resistant to therapy remains a major clinical challenge. In triple-negative breast cancer, resistance to chemotherapy results in the highest recurrence risk among breast cancer subtypes. The drug-tolerant state seems largely defined by nongenetic features, but the underlying mechanisms are poorly understood. Here, by monitoring epigenomes, transcriptomes and lineages with single-cell resolution, we show that the repressive histone mark H3K27me3 (trimethylation of histone H3 at lysine 27) regulates cell fate at the onset of chemotherapy. We report that a persister expression program is primed with both H3K4me3 (trimethylation of histone H3 at lysine 4) and H3K27me3 in unchallenged cells, with H3K27me3 being the lock to its transcriptional activation. We further demonstrate that depleting H3K27me3 enhances the potential of cancer cells to tolerate chemotherapy. Conversely, preventing H3K27me3 demethylation simultaneously to chemotherapy inhibits the transition to a drug-tolerant state, and delays tumor recurrence in vivo. Our results highlight how chromatin landscapes shape the potential of cancer cells to respond to initial therapy.

| S-EPMC7612638 | biostudies-literature

H3K27me3 conditions chemotolerance in triple-negative breast cancer [scChIP-seq]

Project description:H3K27me3 conditions chemotolerance in triple-negative breast cancer [scChIP-seq]

| PRJNA690515 | ENA

H3K27me3 conditions chemotolerance in triple-negative breast cancer [scRNA-seq]

Project description:H3K27me3 conditions chemotolerance in triple-negative breast cancer [scRNA-seq]

| PRJNA691625 | ENA

H3K27me3 conditions chemotolerance in triple-negative breast cancer [ChIP-seq]

Project description:H3K27me3 conditions chemotolerance in triple-negative breast cancer [ChIP-seq]

| PRJNA690561 | ENA

H3K27me3 conditions chemotolerance in triple-negative breast cancer [ChIP-reChIP]

Project description:H3K27me3 conditions chemotolerance in triple-negative breast cancer [ChIP-reChIP]

| PRJNA776903 | ENA

H3K27me3 localization in UTX deficient Plasma cells by CUT&Tag

Project description:To understand the role of the H3K27me3 demethylases, UTX and JMJD3, in B cell differentiation. CUT&Tag for H3K27me3 was performed on CreCtrl and dKO (UTX and JMJD3-deficient) PC at day three post in vivo stimulation with LPS.

2022-02-01 | GSE185098 | GEO

H3K27me3 localization in UTX deficient Plasma cells by CUT&Tag

Project description:H3K27me3 localization in UTX deficient Plasma cells by CUT&Tag

| PRJNA767652 | ENA